This proposal is to request support for a Keystone Symposia meeting entitled Innate Immunity: Mechanisms Linking with Adaptive Immunity, organized by Luke A.J. O'Neill, Kate A. Fitzgerald and Averil I. Ma, which will be held in Dublin, Ireland from June 7 - 12, 2010. In the past 5 years there have been remarkable advances in our understanding of the molecular basis of innate immunity. We now have considerable detail on the major classes of innate immune receptors that sense pathogens and provoke immune and inflammatory responses. These include the Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). The role these receptors play in host defense against microbes has been studied, their signaling pathways elucidated, and their roles in infectious and inflammatory diseases examined in detail. As well as stimulating innate immunity via induction of various effector mechanisms, these receptors also participate in the establishment of adaptive immunity. This occurs via the induction of key cytokines to promote T and B cell development and activation, and also via the induction of co-stimulatory molecules on the surface of dendritic cells, notably CD80 and CD86. A final aspect concerns adjuvancy - microbial or synthetic agents that activate these receptors act as powerful adjuvants required for the establishment of memory responses. The interface between innate and adaptive immunity continues to reveal novel components and mechanisms which might ultimately lend themselves to therapeutic manipulation. New receptors that sense pathogens (particularly nucleic acids) and the mechanisms that activate them are being uncovered. Negative feedback loops from adaptive immunity back to innate immunity are being revealed. Evolutionary aspects are also providing insights into how the complex mammalian immune system was formed. This conference will bring together scientists working on innate immune mechanisms activated by these receptors, and will have as a key focus the ability of these receptors and the responses they elicit to promote adaptive immunity. The conference will therefore be of interest to many investigators interested in immunity and the role the immune system plays in disease. Considerable progress has been made in recent years in our understanding of how microbial invaders are recognized by the innate immune system and how sensing translates into signaling pathways that culminate in the transcriptional regulation of immune response genes. The Keystone Symposia meeting on Innate Immunity: Mechanisms Linking with Adaptive Immunity will bring together world-renowned scientists working on innate immune sensing mechanisms and adaptive immunity, and will be of interest to researchers investigating immunity, infectious disease and the role the immune system plays in autoimmune and inflammatory diseases.